In this proposal we request a console upgrade for a Unity 500 MHz NMR Spectrometer manufactured by Varian Associates. The Unity 500 is three generations out of date and the performance no longer meets the needs of the majority of NIH users within the facility. The upgrade will improve the sensitivity, resolution, and reliability of the current instrument allowing for more sophisticated experiments and higher user throughput. The NMR Facility, which has been in existence for 30 years with a Ph.D. level professional NMR spectroscopist as Director, has a long track record of user training, instrument maintenance, and supervision. The Unity 500 MHz instrument user base consists mostly of faculty with a record of continuous NIH support. Beyond the major users, Cornell currently has three minor users whose groups are young and whose PIs will eventually rely on NIH support. These individuals and their students will use the requested instrumentation for a wide range of health-related projects. Professor B. Ganem (PI) is studying the design of new synthetic prodrugs based on the natural product COTC, which would be targeted specifically to prostate tissue, as well as on the synthesis of new inhibitors of glycosphingolipid metabolism; Professor T.P. Begley will use the instrumentation to study modified enzyme substrates, designed inhibitors, products and mechanistic probes; Professor J. Clardy is investigating fungal metabolites exhibiting anticancer, antiviral, and antibiotic activity; Professor B.R. Crane aims to understand how protein structure controls redox- and photochemistry in biological catalysis and signal transduction. Professor G.W. Coates will investigate new methods for the synthesis of architecturally well-defined biodegradable polymers for biomedical use; Prof. D.B. Collum is investigating organolithium solvation and aggregation states using NMR to obtain new insights into synthetically useful lithium reagents; Professor D.T. McQuade will use NMR in designing new synthetic approaches to highly functionalized polymers; Prof. J. Meinwald will investigate the structures of biologically significant molecules involved in chemical communication.